This K99/R00 award will support the candidate's goal for developing a career as an independent researcher in the field of developmental neuroscience, particularly with regard to the study of dyslexia. The candidate is currently a postdoctoral fellow with considerable research experience in functional and diffusion neuroimaging and has strong computational skills. Training will take place primarily at the University of California, Los Angeles (UCLA) under the primary mentorship of Dr. Arthur Toga, an expert on basic neuroimaging studies, and with the guidance of co-mentor Dr. Katherine Narr, an expert on clinical neuroimaging studies. Additional training will take place at the University of Southern California (USC) under the mentorship of co-mentor Dr. Franklin Manis, an expert on the psychological theories of dyslexia. The training component of this award will focus on three main areas: 1) expanding the candidate's general knowledge about developmental cognitive neuroscience and more specific knowledge regarding current theories relating to dyslexia;2) developing practical skills in acquiring and integrating multimodal neuroimaging data in pediatric cohorts;and 3) developing skills in administering and interpreting the results of neuropsychological tests. Research conducted during the mentored phase of this award will take advantage of an existing longitudinal imaging dataset obtained from prominent investigators in the field of dyslexia to address important hypotheses concerning the systems-level neurobiological correlates of dyslexia prior to reading age or that occur in association with brain maturation during childhood in subjects followed prospectively. Acquisition of structural, functional and diffusion imaging data from new groups of children with dyslexia and reading-level and age-matched controls will be a focus during the R00 phase. During this phase, the candidate will use this independent sample to further develop and apply highly sophisticated multimodal computational image analysis methods to dissociate disturbances in distinct and/or overlapping brain networks that will specifically address the precise nature of reading and writing disturbances in dyslexia. The training plan is designed to fill the gaps in the candidate's previous academic career so that she can successfully attain a tenure-track faculty position at a research university. The research plan is designed to provide insight into the brain mechanisms underlying dyslexia that may help direct more effective behavioral remediation in the future. This work may form an important basis for future studies using cross-modal brain imaging markers to evaluate such remediation approaches in dyslexia. PUBLIC HEALTH RELEVANCE: Relevance to Public Health The ability to read and write fluently has a direct impact on the ability of individuals to meet goals and achieve their full potential, which in turn can have profound effects on their socio-economic status and feelings of self- worth. Developmental dyslexia is a common reading disorder, affecting 5-15% of the population that negatively impacts a child's ability to achieve literacy. The brain mechanisms underlying dyslexia remain incompletely understood, and is it unclear whether specific neurobiological markers may predict dyslexia and/or its prognosis prior to reading age.